Multidimensional Interrogation of the Toxicity–Efficacy Balance in Chinese Medicinal Alkaloids via MOFs, Network Pharmacology, and Chromatography

ABSTRACT Metal–organic frameworks (MOFs) offer a revolutionary platform for addressing the inherent toxicity–efficacy paradox of bioactive alkaloids in traditional Chinese medicine (TCM). This review summarizes recent advances in MOF‐based strategies for detoxification and potentiation of alkaloid drugs by integrating TCM holism principles with modern material science. We emphasize a methodology that combines network pharmacology for in silico prediction of multi‐target mechanisms with chromatographic techniques (e.g., HPLC, LC–MS) for experimental validation of key alkaloids. Using Coptis chinensis against influenza A virus (H1N1) as an example, network pharmacology identifies modulation of TNF‐α and IL‐6 pathways as core mechanisms, while chromatographic analysis confirms and quantifies the predicted bioactive compounds (e.g., berberine and coptisine). This validated multi‐target profile provides a rational basis for designing MOF‐based systems capable of targeted co‐delivery and controlled release of alkaloids, thereby achieving synergistic toxicity reduction and efficacy enhancement. It presents a robust, methodology‐rich framework that bridges computational prediction, analytical validation, and precision delivery for modernizing TCM alkaloid research.